PMID- 34864090
OWN - NLM
STAT- MEDLINE
DCOM- 20220216
LR  - 20220329
IS  - 1879-2650 (Electronic)
IS  - 0005-2728 (Print)
IS  - 0005-2728 (Linking)
VI  - 1863
IP  - 2
DP  - 2022 Feb 1
TI  - Substrate-dependent differential regulation of mitochondrial bioenergetics in the 
      heart and kidney cortex and outer medulla.
PG  - 148518
LID - S0005-2728(21)00151-1 [pii]
LID - 10.1016/j.bbabio.2021.148518 [doi]
AB  - The kinetics and efficiency of mitochondrial oxidative phosphorylation (OxPhos) 
      can depend on the choice of respiratory substrates. Furthermore, potential 
      differences in this substrate dependency among different tissues are not 
      well-understood. Here, we determined the effects of different substrates on the 
      kinetics and efficiency of OxPhos in isolated mitochondria from the heart and 
      kidney cortex and outer medulla (OM) of Sprague-Dawley rats. The substrates were 
      pyruvate+malate, glutamate+malate, palmitoyl-carnitine+malate, 
      alpha-ketoglutarate+malate, and succinate+/-rotenone at saturating concentrations. 
      The kinetics of OxPhos were interrogated by measuring mitochondrial bioenergetics 
      under different ADP perturbations. Results show that the kinetics and efficiency 
      of OxPhos are highly dependent on the substrates used, and this dependency is 
      distinctly different between heart and kidney. Heart mitochondria showed higher 
      respiratory rates and OxPhos efficiencies for all substrates in comparison to 
      kidney mitochondria. Cortex mitochondria respiratory rates were higher than OM 
      mitochondria, but OM mitochondria OxPhos efficiencies were higher than cortex 
      mitochondria. State 3 respiration was low in heart mitochondria with succinate 
      but increased significantly in the presence of rotenone, unlike kidney 
      mitochondria. Similar differences were observed in mitochondrial membrane 
      potential. Differences in H(2)O(2) emission in the presence of succinate+/-rotenone 
      were observed in heart mitochondria and to a lesser extent in OM mitochondria, 
      but not in cortex mitochondria. Bioenergetics and H(2)O(2) emission data with 
      succinate+/-rotenone indicate that oxaloacetate accumulation and reverse electron 
      transfer may play a more prominent regulatory role in heart mitochondria than 
      kidney mitochondria. These studies provide novel quantitative data demonstrating 
      that the choice of respiratory substrates affects mitochondrial responses in a 
      tissue-specific manner.
CI  - Copyright (c) 2021. Published by Elsevier B.V.
FAU - Tomar, Namrata
AU  - Tomar N
AD  - Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee 
      WI-53226, United States of America.
FAU - Zhang, Xiao
AU  - Zhang X
AD  - Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee 
      WI-53226, United States of America.
FAU - Kandel, Sunil M
AU  - Kandel SM
AD  - Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee 
      WI-53226, United States of America.
FAU - Sadri, Shima
AU  - Sadri S
AD  - Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee 
      WI-53226, United States of America.
FAU - Yang, Chun
AU  - Yang C
AD  - Department of Physiology, Medical College of Wisconsin, Milwaukee WI-53226, 
      United States of America.
FAU - Liang, Mingyu
AU  - Liang M
AD  - Department of Physiology, Medical College of Wisconsin, Milwaukee WI-53226, 
      United States of America; Center of Systems Molecular Medicine, Medical College 
      of Wisconsin, Milwaukee WI-53226, United States of America.
FAU - Audi, Said H
AU  - Audi SH
AD  - Department of Biomedical Engineering, Marquette University, Milwaukee WI-53223, 
      United States of America.
FAU - Cowley, Allen W Jr
AU  - Cowley AW Jr
AD  - Department of Physiology, Medical College of Wisconsin, Milwaukee WI-53226, 
      United States of America; Center of Systems Molecular Medicine, Medical College 
      of Wisconsin, Milwaukee WI-53226, United States of America. Electronic address: 
      cowley@mcw.edu.
FAU - Dash, Ranjan K
AU  - Dash RK
AD  - Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee 
      WI-53226, United States of America; Department of Physiology, Medical College of 
      Wisconsin, Milwaukee WI-53226, United States of America; Center of Systems 
      Molecular Medicine, Medical College of Wisconsin, Milwaukee WI-53226, United 
      States of America. Electronic address: rdash@mcw.edu.
LA  - eng
GR  - P01 HL116264/HL/NHLBI NIH HHS/United States
GR  - R01 HL151587/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20211203
PL  - Netherlands
TA  - Biochim Biophys Acta Bioenerg
JT  - Biochimica et biophysica acta. Bioenergetics
JID - 101731706
RN  - BBX060AN9V (Hydrogen Peroxide)
SB  - IM
MH  - *Hydrogen Peroxide
PMC - PMC8957717
MID - NIHMS1789107
OTO - NOTNLM
OT  - Membrane potential
OT  - Mitochondrial bioenergetics
OT  - Oxidative phosphorylation
OT  - ROS production
OT  - Respiration
OT  - Reverse electron transport
OT  - Substrate metabolism
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2021/12/06 06:00
MHDA- 2022/02/17 06:00
PMCR- 2022/03/27
CRDT- 2021/12/05 21:04
PHST- 2021/05/21 00:00 [received]
PHST- 2021/10/29 00:00 [revised]
PHST- 2021/11/20 00:00 [accepted]
PHST- 2021/12/06 06:00 [pubmed]
PHST- 2022/02/17 06:00 [medline]
PHST- 2021/12/05 21:04 [entrez]
PHST- 2022/03/27 00:00 [pmc-release]
AID - S0005-2728(21)00151-1 [pii]
AID - 10.1016/j.bbabio.2021.148518 [doi]
PST - ppublish
SO  - Biochim Biophys Acta Bioenerg. 2022 Feb 1;1863(2):148518. doi: 
      10.1016/j.bbabio.2021.148518. Epub 2021 Dec 3.